mRNA translation;
cap structure;
processing bodies;
mRNA decay;
short interfering RNA;
D O I:
10.1073/pnas.0506482102
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
MicroRNAs (miRNAs) repress translation of target mRNAs by interaction with partially mismatched sequences in their 3' UTR. The mechanism by which they act on translation has remained largely obscure. We examined the translation of mRNAs containing four partially mismatched miRNA-binding sites in the 3' UTR in HeLa cells cotransfected with a cognate miRNA. The mRNAs were prepared by in vitro transcription and were engineered to employ different modes of translation initiation. We find that the 5' cap structure and the 3' poly(A) tail are each necessary but not sufficient for full miRNA-mediated repression of mRNA translation. Replacing the cap structure with an internal ribosome entry site from either the cricket paralysis virus or the encephalomyocarditis virus impairs miRNA-mediated repression. Collectively, these results demonstrate that miRNAs interfere with the initiation step of translation and implicate the cap-binding protein eukaryotic initiation factor 4E as a molecular target.
机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Kitroser, E.
Pomeranz, M.
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机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
Meir Med Ctr, Dept Obstet & Gynecol, IL-44281 Kefar Sava, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Pomeranz, M.
Shochet, G. Epstein
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机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Shochet, G. Epstein
Fishman, A.
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h-index: 0
机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
Meir Med Ctr, Dept Obstet & Gynecol, IL-44281 Kefar Sava, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Fishman, A.
Drucker, L.
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机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Drucker, L.
Sadeh-Mestechkin, D.
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h-index: 0
机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Meir Med Ctr, Dept Obstet & Gynecol, IL-44281 Kefar Sava, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Sadeh-Mestechkin, D.
Lishner, M.
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机构:
Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
Meir Med Ctr, Dept Internal Med A, IL-44281 Kefar Sava, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Lishner, M.
Tartakover-Matalon, S.
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Meir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, IsraelMeir Med Ctr, Oncogenet Lab, IL-44281 Kefar Sava, Israel
机构:
Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
Cardenas, Emilio L.
O'Rourke, Rachel L.
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机构:
Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
O'Rourke, Rachel L.
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h-index:
机构:
Menon, Arya
Meagher, Jennifer
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机构:
Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
Meagher, Jennifer
Stuckey, Jeanne
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机构:
Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA
Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
Stuckey, Jeanne
Garner, Amanda L.
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机构:
Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
机构:
Univ Calif San Francisco, Sch Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA
Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USAUniv Calif San Francisco, Sch Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA
Hsieh, Andrew C.
Ruggero, Davide
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Sch Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA
Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USAUniv Calif San Francisco, Sch Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA